Abstract
BackgroundVitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals.MethodsPlasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof.ResultsPlasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied.ConclusionsPediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency.ImpactWe analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.
Highlights
INTRODUCTION VitaminB12 (cobalamin (Cbl)) is an indispensable water-soluble vitamin that acts as cofactor for the two enzymes methylmalonylCoA mutase and methionine synthase
Plasma MMA was highest in young children, in particular between 1 and 6 months of age, whereas both total Cbl and holoTC were highest from approximately 6 months till 4 years of age and tended to slightly decrease until 10 years of age
Plasma holoTC was correlated to plasma total Cbl; their ratio was independent of age
Summary
INTRODUCTION VitaminB12 (cobalamin (Cbl)) is an indispensable water-soluble vitamin that acts as cofactor for the two enzymes methylmalonylCoA mutase and methionine synthase. Classical symptoms include fatigue and (megaloblastic) anemia Both in adults and children, neurological symptoms (i.e., motor, sensory and cognitive impairments, mood changes, abnormal balance and reflexes, memory loss, stupor, and psychosis) and fatigue can occur before anemia develops and can even exist without hematological symptoms.. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. RESULTS: Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. CONCLUSIONS: Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency
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